T and B lymphocytes play critical roles in the normal immune response. However, aberrant activation of these cells result in a variety of autoimmune disorders and cancers. Activation of T- and B-cells by foreign antigens are mediated by T- and B-cell antigen receptors, respectively, and involves a cascade of biochemical events the culminate in a host response against foreign pathogens. Protein tyrosine kinases (PTKs) play an integral role in T- and B-cell activation and are involved in the initiating events in this cascade. The experiments proposed in this proposal will dissect how the Syk PTK is involved in both T-and B-cell function. This PTK is critical for the development and function of B cells and may also have a role in the function of T cells. An understanding of how the Syk PTK functions in B-cells will provide a greater knowledge of signal transduction mechanisms in lymphocytes and greater insight into regulatory mechanisms of PTKs. In addition, these studies may provide additional mechanistic information that may serve as the basis for more rational therapeutic interventions in drug design for cancer, autoimmune diseases and transplantation rejection.